crossing96/oncoscreening huggingface dataset:
Is the inverse association between selenium and bladder cancer due to confounding by smoking?	Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.	bladder
Perioperative strategies to reduce postoperative complications after radical cystectomy.	Radical cystectomy with creation of urinary diversion is the standard treatment for muscle-invasive urothelial carcinoma of the bladder. Despite advances in perioperative care, radical cystectomy is associated with significant morbidity. Reduction in perioperative morbidity and mortality remains a primary focus of bladder cancer outcome improvement. A number of evidence-based approaches to perioperative care have been proposed to reduce the overall burden of complications associated with radical cystectomy. Herein, we highlight and review recent and evolving evidence-based strategies to minimize the morbidity associated with surgical management of muscle-invasive bladder cancer.	bladder
Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study.	OBJECTIVE: To verify the efficacy and safety of intravesical instillation of pirarubicin combined with hyaluronic acid after TURBT in non-muscle invasive bladder cancer patients. METHODS: We conducted a prospective study recruiting 127 eligible patients from 2008 to 2010. Patients were randomly assigned to Group A (pirarubicin combined with hyaluronic acid) and Group B (pirarubicin alone). Patients' demographics, treatment efficacy on recurrence, visual analog scale score, and postoperative complications were evaluated and analyzed during observation. RESULTS: After the first month of intravesical chemotherapy, a perceptible relief of pelvic pain and urinary symptoms was detectable in Group A when compared with Group B (Fig. 2; P = 0.04). From objective analysis, the clinicians observed a consistent better improvement in Group A than in Group B on clinical conditions (P = 0.02). Frequency, urgency, and odynuria are relieved effectively in Group A (21/64 32.9%) and in Group B (41/63 65.1%), with significant difference observed (P = 0.001). No statistical evidence of benefit was observed in terms of recurrence. No obvious hyaluronic acid-related adverse event was observed. CONCLUSIONS: As compared to intravesical instillation of pirarubicin alone, the administration of pirarubicin combined with HA for prevention from postoperative recurrence was satisfactory and safe. The relief of pelvic pain and urinary symptoms is more rapid and more durable.	bladder
Immune therapies in non-muscle invasive bladder cancer.	Non-muscle invasive bladder cancer (NMIBC) continues to be a challenging disease to manage. Treatment involves transurethral resection and, often, intravesical therapy. Appropriate patient selection, accurate staging, and morphological characterization are vital in risk-stratifying patients to those who would most benefit from receiving intravesical therapy. Bacillus of Calmette and Guérin (BCG) continues to be the first-line agent of choice for patients with intermediate- and high-risk NMIBC. Treatment should begin with the standard induction course of 6 weekly treatments. The inclusion of subsequent maintenance courses of BCG is imperative to optimal therapeutic response. While patients with intermediate-risk disease should receive 1 year of maintenance therapy, high-risk patients benefit from up to 3 years of maintenance therapy. BCG use should not be used in low-risk patients with de novo Ta, low-grade, solitary, <3-cm tumors. Conversely, patients with muscle-invasive disease should forgo intravesical immunotherapy and proceed directly to radical cystectomy. Cystectomy also should be considered in patients with multiple T1 tumors, T1 tumors located in difficult to resect locations, residual T1 on re-resection, and T1 with concomitant CIS. Although promising new immunotherapeutic agents, such as Urocidin, protein-based vaccines, and immune check point inhibitors are undergoing preclinical and clinical investigation, immunotherapy in bladder cancer remains largely reliant on intravesical BCG with surgical consolidation as the standard salvage treatment for patients with BCG failure.	bladder
Biodistribution of Evans blue in an orthotopic AY-27 rat bladder urothelial cell carcinoma model: implication for the improved diagnosis of non-muscle-invasive bladder cancer (NMIBC) using dye-guided white-light cystoscopy.	OBJECTIVES: To investigate the possibility of using Evans blue (EB) as a novel diagnostic tool to detect bladder tumours with white-light (WL) cystoscopy, in this preclinical study we examine the biodistribution of EB in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY-27 tumour cells. MATERIALS AND METHODS: EB was instilled into both normal as well as tumour-bearing rat bladders. After instillation, bladders were removed and snap frozen in liquid nitrogen. The distribution of EB in the different layers was quantified using fluorescence microscopy. To gain more insight into the mechanism underlying the selective accumulation of EB in tumour tissue, bladder sections were prepared for ultrastructural investigations by means of transmission electron microscopy (TEM). In addition, we also examined the expression of E-cadherin, claudin-1 and desmoglein-1 by immunohistochemistry to study the integrity of the bladder wall, as these molecules are key constituents of adherens junctions, tight junctions and desmosomes, respectively. RESULTS: In most cases, the accumulation of EB in malignant bladders was substantially higher than in healthy bladders, at least when 1 mm EB instillations were used. In case of a 1 mm EB instillation for 2 h, the EB-associated fluorescence in malignant urothelial tissue was 55-times higher than the fluorescence found in normal urothelium. Ultrastructurally, malignant tissue displayed wider intercellular spaces and a decreased number of cell junction components compared with normal tissue, pointing to defects in the urothelial barrier. There were no differences in the expression of E-cadherin, whereas desmoglein-1 staining was stronger in the membranes of healthy bladder urothelium compared with tumour tissue. Claudin-1 expression was negative in all samples tested. CONCLUSION: EB is selectively taken up by tumour tissue after intravesical instillations in rats bearing bladder tumours. The lower expression of desmoglein-1 in tumour samples, together with the reduced presence of desmosomes seen with TEM, likely imply that desmosomes play an important role in the ultrastructural differences between healthy rat urothelium and tumour tissue, and secondary to that, to the differential uptake of EB in both tissues. We consider that our findings could be useful for future clinical developments in the field of diagnostics for bladder cancer.	bladder
[Clinical practice and adherence to the diagnosis and treatment of NMIBC guidelines: a report of a recognition based clinical cases study].	For non-muscle invasive bladder cancer, a disease with a considerable epidemiological and socio-economic impact, the introduction of the Guidelines has always evoked as a tool for the resolution of long-standing disputes in terms of diagnosis and therapy. Check the degree of routine clinical practice adherence to the Recommendations is for this disease, more than for other uro-oncology pathology, an urgent need felt by the urological community. To assess the level of Guidelines adherence's, and study issues related to the paths of diagnosis and treatment of non-muscle invasive bladder cancer, and identifying the processes actually implemented in daily clinical practice, a series of case studies has submitted to a group of experts. The acknowledgement study allowed testing the impact of the current Evidence Based Medicine Recommendations in the everyday clinical practice identifying strengths and weaknesses. Questions Responses Analysis' of 5 clinical cases (Ta low grade, T1 low grade, T1 high grade, T1 high grade + CIS, Ta low-grade multiple recurrence) showed a moderate amendment to the European Association of Urology (EAU)-Guidelines. On the other hand, it was emphasized that there are clear discrepancies between what should be done, in accordance with the Evidence Based Medicine Recommendations, and what is actually do in everyday clinical practice. The most common reason for the low Recommendations adherences are structural and organizational practical limitations.	bladder
Urethral recurrence in women with orthotopic bladder substitutes: A multi-institutional study.	OBJECTIVES: To evaluate risk factors for urethral recurrence (UR) in women with neobladder. MATERIAL AND METHODS: From 1994 to 2011, 297 women (median age = 54 y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116). RESULTS: Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumor involvement was present in 60 patients (20.2%). On univariable and multivariable analyses, pathologic tumor and nodal stage were independent predictors for the overall risk of recurrence. UR was associated with a positive final urethral margin status (P<0.001) whereas no significant associations were found for carcinoma in situ, pathologic tumor and nodal stage, and bladder trigone involvement. CONCLUSIONS: In this series, only 0.6% of women developed solitary UR. A positive final urethral margin was associated with an increased risk of UR. Women with involvement of the bladder trigone were not at higher risk of UR.	bladder
Effect of hypertension on outcomes of high-risk patients after BCG-treated bladder cancer: a single-institution long follow-up cohort study.	"Immunotherapy with Bacillus Calmette-Guérin (BCG) is the most efficacious treatment for high-risk bladder cancer (BC) (Ta/T1 or carcinoma in situ) to reduce the risk of recurrence. Our aim was to evaluate whether hypertension and diabetes influence the outcome of patients with noninvasive BC treated with BCG instillations.In order to collect homogeneous data, we considered as ""hypertensive"" only those patients who had previous diagnosed hypertension and a history of taking medical therapy with antihypertensive drugs (AHT), and as ""diabetic"" only those prescribed oral antidiabetics or insulin (ADT).We analyzed 343 high-risk BC patients undergoing BCG (1995-2010) with a median follow-up of 116 months (range 48-238). The distribution of various kinds of AHT and antidiabetic drugs was homogeneous, with no significant differences (p > 0.05).In both univariate and multivariate analyses, the only statistically significant parameter prognostic for recurrence after BCG treatment was AHT. Recurrence-free survival curves showed a significant correlation with AHT (p = 0.0168, hazards ratio [HR] 1.45, 95% confidence interval [CI] 1.0692-1.9619); there was no correlation (p = 0.9040) with ADT (HR 0.9750, 95% CI 0.6457-1.4721). After stratification of AHT and ADT according to drug(s) prescribed, there were no significant differences in the BC recurrence rate (p > 0.05).In this study with a very long-term follow-up, hypertension alone (evaluated by AHT) revealed the increased risk of BC recurrence after BCG treatment.Several hypotheses have been formulated to support these findings, but further prospective studies are needed to both evaluate the real influence of hypertension and identify a possible prognostic factor to be used in selecting poor-prognosis BC patients as early candidates for surgical treatment."	bladder
Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma.	"OBJECTIVE: To evaluate programmed death ligand 1 (PD-L1) expression in urothelial carcinoma of the bladder in relationship with tumor-infiltrating CD8+ T cells. MATERIALS AND METHODS: Tissue microarrays were prepared from 56 cystectomy specimens performed at our hospital (1994-2002). PD-L1 immunoexpression was assessed using the murine antihuman PD-L1 monoclonal antibody 5H1. Extent of membranous PD-L1 expression was assigned in each spot. Spots showing ≥5% expression were considered positive. Average PD-L1 expression per tumor was also calculated (5% positivity cutoff). ""High CD8 density"" was defined as the presence of ≥60 CD8+ intraepithelial lymphocytes per high power field in a given spot. A tumor was considered high density if ≥50% of its spots were of high density. RESULTS: PD-L1 expression was positive in approximately 20% of tumors. None of the benign urothelium spots expressed PD-L1. High CD8 density was observed in approximately 20% of cases. CD8 density did not correlate with PD-L1 expression. Overall survival (OS) and disease-specific survival (DSS) rates were 14% and 28%, respectively (median follow-up, 31.5 months). PD-L1 expression was associated with age at cystectomy (P = .01). Remaining clinicopathologic parameters were not associated with PD-L1 expression or CD8 density. High CD8 density was associated with favorable OS (P = .02) and DSS (P = .02). The same was true when CD8 density was adjusted for demographic and clinicopathologic parameters. There was no correlation between PD-L1 expression and outcome. CONCLUSION: High intratumoral CD8+ T cell density is associated with better OS and DSS in invasive urothelial carcinoma of the bladder. We found no correlation between PD-L1 expression and outcome."	bladder
[Transurethral resection of a intravesical recurrence of a tumor after resection of sigmoid colon cancer].	A 66-year-old man presented to the urology clinic with hematuria. Cystoscopy with biopsy was performed for suspected bladder cancer, and a pathological diagnosis of adenocarcinoma was made. Colonoscopy revealed sigmoid colon cancer, and he was referred to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) showed sigmoid colon cancer with urinary bladder invasion. Sigmoidectomy with lymph node dissection and partial cystectomy were performed under laparotomy. The pathological diagnosis was moderately differentiated adenocarcinoma: T4b (bladder), N1, M0, and the bladder margin was negative. Four months after surgery, CT revealed a small mass in the bladder. Cystoscopy showed a papillary pedunculated tumor at the bladder trigone, and a transurethral resection was performed. Pathological examination revealed a moderately differentiated adenocarcinoma, similar to the prior sigmoid colon cancer, which was diagnosed as an intravesical recurrence of the tumor. More than 8 years after the transurethral resection, the patient has shown no signs of recurrence.	bladder
P70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression in orthotopic mouse non-muscle invasive bladder tumor model.	We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 µM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.	bladder
Is intravesical Bacillus Calmette-Guérin therapy superior to chemotherapy for intermediate-risk non-muscle-invasive bladder cancer? An ongoing debate.	The objective of this study was to evaluate the risk of recurrence in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) after intravesical instillation with chemotherapeutic agents or Bacillus Calmette-Guérin (BCG) therapy. A cohort of 746 patients with intermediate-risk NMIBC comprised the study group. The primary outcome was time to first recurrence. The recurrence rates of the transurethral resection (TUR) alone, chemotherapy, and BCG groups were determined using Kaplan-Meier analysis. Risk factors for recurrence were identified using Cox regression analysis. In total, 507 patients (68.1%), 78 patients (10.5%), and 160 (21.4%) underwent TUR, TUR+BCG, or TUR+chemotherapy, respectively. After a median follow-up period of 51.7 months (interquartile range=33.1-77.8 months), 286 patients (38.5%) developed tumor recurrence. The 5-yr recurrence rates for the TUR, chemotherapy, and BCG groups were 53.6%±2.7%, 30.8%±5.7%, and 33.6%±4.7%, respectively (P<0.001). Chemotherapy and BCG treatment were found to be predictors of reduced recurrence. Cox-regression analysis showed that TUR+BCG did not differ from TUR+chemotherapy in terms of recurrence risk. Adjuvant intravesical instillation is an effective prophylactic that prevents tumor recurrence in intermediate-risk NMIBC patients following TUR. In addition, both chemotherapeutic agents and BCG demonstrate comparable efficacies for preventing recurrence.	bladder
Sonic hedgehog (Shh) signaling promotes tumorigenicity and stemness via activation of epithelial-to-mesenchymal transition (EMT) in bladder cancer.	Activation of the sonic hedgehog (Shh) signaling pathway controls tumorigenesis in a variety of cancers. Here, we show a role for Shh signaling in the promotion of epithelial-to-mesenchymal transition (EMT), tumorigenicity, and stemness in the bladder cancer. EMT induction was assessed by the decreased expression of E-cadherin and ZO-1 and increased expression of N-cadherin. The induced EMT was associated with increased cell motility, invasiveness, and clonogenicity. These progression relevant behaviors were attenuated by treatment with Hh inhibitors cyclopamine and GDC-0449, and after knockdown by Shh-siRNA, and led to reversal of the EMT phenotype. The results with HTB-9 were confirmed using a second bladder cancer cell line, BFTC905 (DM). In a xenograft mouse model TGF-β1 treated HTB-9 cells exhibited enhanced tumor growth. Although normal bladder epithelial cells could also undergo EMT and upregulate Shh with TGF-β1 they did not exhibit tumorigenicity. The TGF-β1 treated HTB-9 xenografts showed strong evidence for a switch to a more stem cell like phenotype, with functional activation of CD133, Sox2, Nanog, and Oct4. The bladder cancer specific stem cell markers CK5 and CK14 were upregulated in the TGF-β1 treated xenograft tumor samples, while CD44 remained unchanged in both treated and untreated tumors. Immunohistochemical analysis of 22 primary human bladder tumors indicated that Shh expression was positively correlated with tumor grade and stage. Elevated expression of Ki-67, Shh, Gli2, and N-cadherin were observed in the high grade and stage human bladder tumor samples, and conversely, the downregulation of these genes were observed in the low grade and stage tumor samples. Collectively, this study indicates that TGF-β1-induced Shh may regulate EMT and tumorigenicity in bladder cancer. Our studies reveal that the TGF-β1 induction of EMT and Shh is cell type context dependent. Thus, targeting the Shh pathway could be clinically beneficial in the ability to reverse the EMT phenotype of tumor cells and potentially inhibit bladder cancer progression and metastasis.	bladder
Preoperative imaging for staging bladder cancer.	Accurate preoperative staging of bladder cancer is essential in determining the extent of disease and optimal treatment. The current gold standard of transurethral resection of bladder tumor (TURBT) followed by computed tomography (CT) imaging provides excellent staging specificity, but often understages the disease, leading to pathologic upstaging and adverse outcomes in patients undergoing radical cystectomy. Newer imaging modalities, such as multiparametric magnetic resonance (MR) imaging and positron emission tomography (PET) combined with CT or MR provides promising imaging alternatives which may improve accuracy of staging both local and distant disease.	bladder